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Biomedical subjects

D Brown

Publications and source records attributed to D Brown.

At least 397 records · Page 22Linked to original sources
PubMed1996

Prevalence of hepatitis C in patients with primary antibody deficiency.

Concern over sporadic hepatitis C virus (HCV) infection from treatment with contaminated immunoglobulin in patients with immunodeficiency prompted use to screen serum from 44 patients for HCV RNA. We found no evidence of either horizontal or iatrogenic infection in our Clinic, except in two patients known to have received contaminated batches, and in one who had had regular plasma infusions. Thus, common variable immunodeficiency (CVID) patients in England do not have a high incidence of HCV infection despite exposure to various immunoglobulin products. This contrasts with the recently reported high prevalence in similar patients in Italy. Although our data reinforce the impression that both intramuscular and current licensed i.v. preparations in the UK are safe, manufacturers should be encouraged to PCR screen all batches of immunoglobulin for HCV.

Agammaglobulinemia↗
PubMed1996

Incidence, character and clinical relevance of mixed cryoglobulinaemia in patients with chronic hepatitis C virus infection.

Hepatitis C virus (HCV) infection has been implicated in the pathogenesis of mixed cryoglobulinaemia. Several studies have shown the presence of anti-HCV antibodies and HCV-RNA in both sera and cryoglobulins of such patients. However, the prevalence and clinical significance of cryoglobulins remain uncertain in patients with chronic HCV infection. We have studied 113 consecutive patients referred for assessment because of the presence of anti-HCV antibody in serum for the presence of cryoglobulinaemia and ascertained their clinical relevance and immunochemical properties. Twenty-one of 113 (19%) had detectable cryoglobulins with a mean protein concentration of 0.38 g/l (range 0.15-3.34 g/l). Most of these patients were asymptomatic. The cryoglobulins were of type III in 19 (91%) and of type II in two patients (9%). The latter two patients had the highest concentration of cryoglobulins, subnormal C4 and C1q levels suggesting classical pathway activation and vasculitis with renal impairment. The cryoglobulin IgG subclasses were mainly IgG1 and IgG3. HCV-RNA was detected more frequently in the sera of cryoglobulin-positive patients than in cryoglobulin-negative patients. This study showed that mixed cryoglobulinaemia is common in chronic HCV infection, and is predominantly type III. Evidence of systemic or renal disease was rare except in those with type II cryoglobulinaemia, and this may reflect either the concentration of the cryoprecipitate or the presence of a monoclonal complement-activating IgM paraprotein. The detection of HCV-RNA in the majority of the cryoprecipitates further supports the important role of HCV in the etiopathogenesis of essential mixed cryoglobulinaemia, although the mechanism is at present unclear.

Adult↗
PubMed1996

Optimized and corrected peak power output during friction-braked cycle ergometry.

Assessments of maximal intensity exercise which determine peak power output on friction-baked cycle ergometers have fallen into two categories: correction procedures which account for changes in momentum of the ergometer's flywheel and optimization procedures which attempt to satisfy muscle force-velocity relationships. The aim of this study was to compare performance in each procedure and so investigate assumptions which underpin the tests. Nineteen males aged 20.9 +/- 0.4 years and 18 females aged 22.2 +/- 0.7 years (mean +/- S.E.M.), who were fully accustomed to the procedures, participated in a single experimental protocol. After a 5 min warm-up, the subjects performed four bouts of all-out exercise on a Monark 814E cycle ergometer against randomly assigned loads. The loads were selected to produce peak pedalling rates in the range 100-200 rev min-1 and each bout lasted 10 s. From the inverse linear relationship between applied load and peak pedalling rate, optimized peak power output (PPopt) and the accompanying pedalling rate (RPMopt) were calculated. One of the bouts used a loading equivalent to 7.5% of body weight and for this bout corrected peak power output (PPcorr) and its corresponding pedalling rate (RPMcorr) were calculated. The PPopt was less than PPcorr in the males (915 +/- 35 vs 1005 +/- 32 W) and females (673 +/- 33 vs 777 +/- 39 W) (both P < 0.001). Similarly, RPMopt was less than RPMcorr (111 +/- 1 vs 128 +/- 2 rev min-1 and 101 +/- 1 vs 111 +/- 2 rev min-1 in the males and females, respectively; P < 0.001). The results demonstrate that optimization and correction procedures produce different values of performance. These differences are probably attributable to the mechanical principles which underpin the tests.

Adult↗
PubMed1996

Molecular epidemiology of measles virus: identification of pathways of transmission and implications for measles elimination.

The nucleotide sequences of either the hemagglutinin or nucleoprotein genes from wild type measles viruses isolated in the United States between 1989 and 1992 differed by < 0.5%. This suggests that the majority of viruses associated with resurgence of measles in the United States belonged to a single indigenous genotype. In contrast, wild type viruses isolated from sporadic outbreaks of measles in the United States during 1994 were genetically heterogeneous. These viruses were more closely related to wild type viruses previously circulating in Europe, Africa, or Japan and were epidemiologically linked to importations or no known source. In addition to demonstrating the utility of genetic analysis in understanding the epidemiology of measles, these data suggest that the transmission of the indigenous virus was interrupted after the 1989-1992 epidemic. Measures to further reduce the incidence of measles in the United States should include efforts to control importation and subsequent spread of measles.

Base Sequence↗
PubMed1996

Hospital admissions attributable to rotavirus infection in England and Wales.

Laboratory reports and data on hospital admissions were used to estimate the number of hospitalizations due to group A rotavirus infection in England and Wales. Between January 1990 and December 1994, there were 75,059 laboratory reports of rotavirus infection, and 66,062 of these were in children <5 years old; rotavirus represented 39% of all pathogens identified in fecal specimens from this age group. Between April 1993 and March 1994, 1904 hospital admissions coded as "infectious intestinal disease" and 2354 coded as "noninfective gastroenteritis" occurred in children <5 in the North Thames region (a health authority representing 13% of the population in England and Wales). By modeling admission and laboratory reporting data, it was estimated that 54% of hospitalizations for intestinal infectious disease and 34% for noninfective gastroenteritis were attributable to rotavirus. By extrapolation of the North Thames data, it was estimated that 17,810 rotavirus-related hospitalizations (5/1000 children <5 years old) occurred in England and Wales during the same period. Effective vaccines have the potential to substantially reduce the number of hospital admissions due to group A rotavirus infection.

Adolescent↗
PubMed1996

Flap selection in cranial base reconstruction.

We have compared our local, pedicled, and free-flap reconstructions for 90 skull base defects performed over the past 10 years. The pericranial flap was found to provide a reliable dural seal. Free-flap reconstructions exhibited a significantly higher incidence of uncomplicated primary wound healing (95 versus 62.5 percent) and a much lower incidence of flap loss (0 percent), cerebrospinal fluid leak (5 percent), meningitis, and abscess (0 percent) when compared with defects reconstructed with pedicled myocutaneous flaps. We conclude that microvascular free-tissue transfer is the safest, most economical procedure when faced with moderate to large composite defects of the cranial base.

Female↗
PubMed1996

Longitudinal genotype analysis and quantification of hepatitis C virus in haemophilic patients receiving interferon-alpha therapy.

Haemophilic patients have a high prevalence of hepatitis C virus (HCV) infection because of the use of unsterilized clotting factor concentrates. Six major genotypes of HCV have been distinguished so far, with epidemiological evidence suggesting that genotypes 1-3 are common in the indigenous UK and US populations. The aim of this study was to analyse the changes in viral load and composition of the HCV quasispecies in haemophilic patients receiving therapy with interferon-alpha (IFN-alpha) using the four major methods currently available for HCV genotyping. The most consistent genotype results were obtained using restriction fragment-length polymorphism (RFLP) analysis when compared with the DNA sequence analysis, and showed that the dominant genotype can change in patients with mixed genotype infections treated with IFN-alpha. This study indicates the difficulties in studying this group of patients with mixed HCV genotype infections, and that frequent sampling is necessary, together with viral load measurement to monitor response to IFN-alpha therapy.

Adult↗
PubMed1996

Gender representation in illustrations, text, and topic areas in sexuality education curricula.

A content analysis instrument was developed to examine differences in gender representation in sexuality education curricula. Fourteen middle school and high school curricula, published between 1985 and 1995, were examined. Variables included illustrations, noun/pronoun usage, and specific topics within the two categories of biological function and mutual interest. The study examined differences in gender representation in illustrations, photographs, cartoons, drawings, and text. Omission of sexuality topics related to gender also was examined. Little difference occurred within the text of the curricula in noun and pronoun usage. Illustrations were few in number, but showed greater female representation. Greater male representation occurred in topics related to drug use, sexual exploitation, sexual desire, and homosexuality. Topics with greater female representation included body image, diseases of the reproductive organs, and hygiene.

Books, Illustrated↗
PubMed1996

Tetanus immunisation in the elderly population.

OBJECTIVE: To emphasise that tetanus still occurs in the United Kingdom, particularly in elderly people-as illustrated by two case reports-and to examine the state of tetanus immunity in elderly people. METHODS: 111 elderly people (over 65 years) were studied: 43 males, mean age 77.7 years, range 67-94; 68 females, mean age 81.3 years, range 67-95. They were either attending the accident service or were hospital inpatients. An attempt was made to obtain an immunisation history and antitetanus antibody titres were measured. RESULTS: Immunisation history was uncertain and unreliable. Measurement of antibody titres showed that they were inadequate to ensure protection in 50% of those studied. Low levels were particularly prevalent in the over 80 age group and in females. Questioning about military service confirmed that this had predominantly involved males. CONCLUSIONS: Elderly people are at risk of contracting tetanus and should be targeted for community immunisation. Extra precautions in the form of passive immunisation with human anti-tetanus immunoglobulin should be used in this age group in addition to the usual wound management measures when the elderly sustain tetanus prone injuries.

Age Factors↗
PubMed1996

Localization of parathyroid hormone/parathyroid hormone-related peptide receptor mRNA in kidney.

In kidney, parathyroid hormone (PTH) exerts differential distal effects along the nephron. To define cells expressing receptors for PTH in kidney, we localized PTH/ PTH-related peptide (PTH/PTHrP) receptor mRNA in rat kidney by in situ hybridization. PTH/PTHrP receptor mRNA is localized to glomerular podocytes, convoluted and straight proximal tubules, the cortical portion of thick ascending limbs, and distal convoluted tubules, but was not detected in the thin limb of Henle's loop or in collecting ducts. Northern blot analysis showed that cultured human glomerular podocytes express a unique 4.0-kb PTH/PTHrP receptor transcript but do not express detectable levels of the common approximately 2.4-kb transcript found in whole kidney and in many other tissues. Whereas the tubular localization of PTH/PTHrP receptor mRNA coincides well with previously known sites of PTH action, the intense expression and the unique size of the PTH/PTHrP receptor transcript in glomerular podocytes suggest that PTH and/or PTHrP may play a role(s) in glomerular function.

Autoradiography↗
PubMed1996

Direct demonstration of aquaporin-2 water channel recycling in stably transfected LLC-PK1 epithelial cells.

Vasopressin-dependent membrane insertion of aquaporin-2 (AQP-2) in collecting duct principal cells has been demonstrated in vivo and in vitro. However, the hypothesis that the AQP-2 molecule recycles between intracellular vesicles and the plasma membrane in response to hormonal stimulation and withdrawal remains to be demonstrated directly. In the present study, we examined AQP-2 recycling between intracellular vesicles and the plasma membrane in the absence of de novo protein synthesis using LLC-PK1 cells transfected with an AQP-2-c-myc construct. Cells were treated with cycloheximide for 30 min prior to vasopressin stimulation, and all subsequent treatments were performed in the continued presence of cycloheximide. Complete inhibition of AQP-2 biosynthesis by cycloheximide was verified by immuno-precipitation. Immunofluorescence revealed that AQP-2 was located on intracellular vesicles in nonstimulated cells but was relocated to the plasma membrane after vasopressin treatment, even in the presence of cycloheximide. After vasopressin washout, AQP-2 was retrieved to intracellular vesicles and was relocated to the plasma membrane after restimulation with forskolin. Subsequent forskolin washout resulted in AQP-2 endocytosis, and a second stimulation with forskolin resulted in relocation to the plasma membrane. These data, obtained in the absence of de novo protein synthesis, clearly indicate that AQP-2 can be recycled multiple times between intracellular vesicles and the plasma membrane.

Animals↗
PubMed1996

Specific effect of maleate on an apical membrane glycoprotein (gp330) in proximal tubule of rat kidneys.

Maleate treatment of rats induces transport defects similar to those seen in the Fanconi syndrome (glycosuria, aminoaciduria, phosphaturia, proteinuria, etc.) and causes an accumulation of apical vesicles in proximal tubule epithelial cells. Because the apical membrane glycoprotein, gp330, is a receptor associated with the apical endocytotic and recycling apparatus in these cells, we examined the effect of maleate on the distribution of this protein and other brush border markers. Rats received sodium maleate (400 mg/kg ip) and were killed at various times between 45 min and 3 h; kidneys were perfusion fixed with paraformaldehyde-lysine-periodate before processing for immunofluorescence and immunoelectron microscopy. In control rats, staining with a polyclonal or monoclonal gp330 antibody showed a uniform distribution on the brush border and in coated pits of all proximal tubule cells. In the S3 segments, the immunofluorescence labeling of the microvilli was generally uniform but at times showed spike labeling, suggesting that gp330 sheds easily from the apical membrane. After maleate treatment, the staining intensity of the brush border was decreased in all proximal tubule segments, and cytoplasmic streaks as well as an intense vacuolar staining were seen. In the S3 segment, a remarkable mosaic pattern of staining was observed, with the brush border of some cells being completely negative, while adjacent cells showed an apparently normal staining pattern. These results were confirmed at the electron microscope level, using the protein A-gold technique. Maleate had no effect on the distribution or staining intensity of four other brush border markers, dipeptidyl peptidase IV, and various lectins (Helix pomatia lectin, peanut lectin, elderberry bark lectin). The urinary excretion of gp330 occurs in normal rats and was already increased as early as 1 h after maleate injection and remained at a twofold increment between 6 and 24 h. These data suggest that the generalized membrane transport derangement seen in this experimental Fanconi syndrome could occur via a specific effect on gp330, which seems to block endocytosis and the recycling apparatus at the late endosome level and inhibits the formation of new dense apical tubules.

Animals↗
PubMed1996

Protein trafficking and polarity in kidney epithelium: from cell biology to physiology.

The transepithelial movement of fluids, electrolytes, and larger molecules is achieved by the activity of a host of specialized transporting proteins, including enzymes, receptors, and channels, that are located on either the apical, basal, or lateral plasma membrane domains of epithelial cells. In the kidney as well as in all other organs, this remarkable polarity of epithelial cells depends on the selective insertion of newly synthesized and recycling proteins and lipids into distinct plasma membrane domains and on the maintenance and modulation of these specialized domains once they are established during epithelial development. This review addresses the mechanisms by which epithelial cells control the movement of membrane components within the cell to ensure that they are delivered to the correct target membrane. Among the topics discussed are targeting signals within membrane proteins, the role of the cytoskeleton and the tight junctional barrier in cell polarity, and the requirement for accessory proteins in the targeting process, including GTP-binding proteins, and proteins that are involved in vesicle docking and fusion events. The final part of the review is devoted uniquely to the polarized targeting of functionally defined proteins in various kidney cell types. In concluding, examples of how a breakdown in these trafficking pathways may be related to some disease states are presented.

Animals↗